NIR/pH-triggered aptamer-functionalized DNA origami nanovehicle for imaging-guided chemo-phototherapy

Mengyue Li; Geng Yang; Yue Zheng; Jiazhen Lv; Wanyi Zhou; Hanxi Zhang; Fengming You; Chunhui Wu; Hong Yang; Yiyao Liu

doi:10.1186/s12951-023-01953-9

Journal of Nanobiotechnology (Jun 2023)

NIR/pH-triggered aptamer-functionalized DNA origami nanovehicle for imaging-guided chemo-phototherapy

Mengyue Li,
Geng Yang,
Yue Zheng,
Jiazhen Lv,
Wanyi Zhou,
Hanxi Zhang,
Fengming You,
Chunhui Wu,
Hong Yang,
Yiyao Liu

Affiliations

Mengyue Li: Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China
Geng Yang: Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China
Yue Zheng: Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China
Jiazhen Lv: Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China
Wanyi Zhou: Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China
Hanxi Zhang: Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China
Fengming You: TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu, University of Traditional Chinese Medicine
Chunhui Wu: Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China
Hong Yang: Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China
Yiyao Liu: Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China

DOI: https://doi.org/10.1186/s12951-023-01953-9
Journal volume & issue: Vol. 21, no. 1
pp. 1 – 14

Abstract

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Abstract Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier’s endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.

Published in Journal of Nanobiotechnology

ISSN: 1477-3155 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Technology: Chemical technology: Biotechnology; Medicine: Medicine (General): Medical technology
Website: https://jnanobiotechnology.biomedcentral.com/

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